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Peer-reviewedCC BY-NC-NDNature communications

Single-oocyte proteome-transcriptome co-profiling reveals a role of dysregulated lactate metabolism in oocyte aging.

  • Lanrui Cao1
  • Hao Wu1
  • Yirong Jiang1,2
  • Yaxue Hou1
  • Zhuo Yang3
  • Yuan Wang4
  • Peipei Ren5
  • Panpan Zhao5
  • Xiaofeng Ni2
  • Shuai Liu6
  • Na Kong6
  • Xin Sheng6
9 more authors
  • Yinli Zhang5
  • Songying Zhang5
  • Jianfeng Xiao7
  • Cunqi Ye4
  • Heng-Yu Fan5
  • Yongcheng Wang8
  • Xiaomei Tong9
  • Qun Fang10,11,12
  • Xudong Fu13,14,15
15 affiliations
  1. 1First Affiliated Hospital, Zhejiang University School of Medicine, and Liangzhu Laboratory of Zhejiang University, Hangzhou, China.
  2. 2Institute of Microanalytical Systems, Department of Chemistry, Key Laboratory of Excited-State Materials of Zhejiang Province, Zhejiang University, Hangzhou, China.
  3. 3School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China.
  4. 4Zhejiang Provincial Key Laboratory for Cancer Molecular Cell Biology, Life Sciences Institute, Zhejiang University, Hangzhou, China.
  5. 5Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
  6. 6Liangzhu Laboratory of Zhejiang University, Hangzhou, China.
  7. 7Department of Reproductive Center, The First Affiliated Hospital of Shantou University Medical College, Shantou University, Shantou, China.
  8. 8First Affiliated Hospital, Zhejiang University School of Medicine, and Liangzhu Laboratory of Zhejiang University, Hangzhou, China. [email protected].
  9. 9Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China. [email protected].
  10. 10Institute of Microanalytical Systems, Department of Chemistry, Key Laboratory of Excited-State Materials of Zhejiang Province, Zhejiang University, Hangzhou, China. [email protected].
  11. 11Single-cell Proteomics Research Center, ZJU-Hangzhou Global Scientific and Technological Innovation Center, Hangzhou, China. [email protected].
  12. 12Key Laboratory for Biomedical Engineering of Ministry of Education, Cancer Center, Zhejiang University, Hangzhou, China. [email protected].
  13. 13First Affiliated Hospital, Zhejiang University School of Medicine, and Liangzhu Laboratory of Zhejiang University, Hangzhou, China. [email protected].
  14. 14Institute of Hematology, Zhejiang University, Hangzhou, China. [email protected].
  15. 15Department of Geriatrics, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. [email protected].
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Abstract

The age-related decline in oocyte quality is a major risk factor for female infertility. Although transcriptome has been examined in aged oocytes, proteomic landscape, which reflects primary gene functional executors, remains largely unexplored. This gap limits our understanding of oocyte aging. To address this, we perform single-cell proteome/transcriptome co-profiling of GV/MII-aged oocytes from mice and humans, revealing species- and stage-specific proteomic/transcriptomic changes during oocyte aging. Strikingly, we observe uncoupled proteomic and transcriptomic alterations, indicating that proteomic changes in aged oocytes are not primarily driven by RNA levels. Furthermore, we capture molecular heterogeneity in aged oocytes and identify MCT4 as a candidate marker of oocyte aging. Functional studies suggest MCT4 contributes to aging-associated oocyte defects via lactate export, and its inhibition improves aged-oocyte quality. These findings indicate altered lactate metabolism as a candidate marker and intervention target for oocyte aging and underscore the value of our profiling in dissecting oocyte aging.

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Cite

BibTeXRIS
BibTeX
@article{cao2026singleoocyte,
  title = {{Single-oocyte proteome-transcriptome co-profiling reveals a role of dysregulated lactate metabolism in oocyte aging.}},
  author = {Lanrui Cao and Hao Wu and Yirong Jiang and Yaxue Hou and Zhuo Yang and Yuan Wang and Peipei Ren and Panpan Zhao and Xiaofeng Ni and Shuai Liu and Na Kong and Xin Sheng and Yinli Zhang and Songying Zhang and Jianfeng Xiao and Cunqi Ye and Heng-Yu Fan and Yongcheng Wang and Xiaomei Tong and Qun Fang and Xudong Fu},
  journal = {Nature communications},
  year = {2026},
  month = sep,
  doi = {10.1038/s41467-026-77910-5},
  url = {https://europepmc.org/article/MED/42901925},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - Single-oocyte proteome-transcriptome co-profiling reveals a role of dysregulated lactate metabolism in oocyte aging.
AU  - Lanrui Cao
AU  - Hao Wu
AU  - Yirong Jiang
AU  - Yaxue Hou
AU  - Zhuo Yang
AU  - Yuan Wang
AU  - Peipei Ren
AU  - Panpan Zhao
AU  - Xiaofeng Ni
AU  - Shuai Liu
AU  - Na Kong
AU  - Xin Sheng
AU  - Yinli Zhang
AU  - Songying Zhang
AU  - Jianfeng Xiao
AU  - Cunqi Ye
AU  - Heng-Yu Fan
AU  - Yongcheng Wang
AU  - Xiaomei Tong
AU  - Qun Fang
AU  - Xudong Fu
PY  - 2026
DA  - 2026/09/21
JO  - Nature communications
DO  - 10.1038/s41467-026-77910-5
UR  - https://europepmc.org/article/MED/42901925
AB  - The age-related decline in oocyte quality is a major risk factor for female infertility. Although transcriptome has been examined in aged oocytes, proteomic landscape, which reflects primary gene functional executors, remains largely unexplored. This gap limits our understanding of oocyte aging. To address this, we perform single-cell proteome/transcriptome co-profiling of GV/MII-aged oocytes from mice and humans, revealing species- and stage-specific proteomic/transcriptomic changes during oocyte aging. Strikingly, we observe uncoupled proteomic and transcriptomic alterations, indicating that proteomic changes in aged oocytes are not primarily driven by RNA levels. Furthermore, we capture molecular heterogeneity in aged oocytes and identify MCT4 as a candidate marker of oocyte aging. Functional studies suggest MCT4 contributes to aging-associated oocyte defects via lactate export, and its inhibition improves aged-oocyte quality. These findings indicate altered lactate metabolism as a candidate marker and intervention target for oocyte aging and underscore the value of our profiling in dissecting oocyte aging.
SN  - 2041-1723
ER  -